Phase I Study of Intra-Tumoral Injections of Autologous Ex Vivo Expanded Natural Killer Cells in Children With Recurrent High Grade Glioma

STUDY00000659

Patients will receive 3 cycles of NK cell infusions over 12 weeks. Each cycle will consist of 1 infusion per week for 3 weeks, followed by a rest week (week 4). Dose will be escalated in an inter-patient stepwise fashion consisting of 4 dose levels.

2023-12-01

2024-10-01

2025-10-01

Not yet recruiting

Early phase I

24

Inclusion Criteria: 1. Patients must have a histologically-confirmed recurrent non-metastatic supratentorial WHO Grade III malignant glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, and anaplastic pleomorphic xanthoastrocytoma) or WHO Grade IV malignant glioma (glioblastoma multiforme, gliosarcoma, malignant glioma NOS) 2. Patients should be candidates for resection/open biopsy of the recurrent tumor and be deemed candidate for placement of an Ommaya reservoir placed intra-cavitary/ intra-tumoral; measurable residual tumor after surgery is not required for study entry 3. Given the lack of a standard of care treatment for children with recurrent grade III/IV gliomas, patients must have completed first-line treatment with 54 Gy of radiation prior to participating in this trial 4. All patients must be ≥ 3 years of age and \<18 years of age at the time of study entry into the study 5. Lansky score of 50 or greater if ≤ 16 years of age or a Karnofsky score of 50 or greater if \>16 years of age 6. Adequate bone marrow function, without transfusion or growth factors within 21 days of NK cell administration, defined as a white blood cell ≥ 2.5 x 103/microliter, hemoglobin ≥ 9 gm/dL, absolute neutrophil count ≥ 1,000 cells/microliter and platelet count of ≥ 75,000 cells/microliter 7. Patients must be off systemic steroids (except replacement therapy) for at least 3 days prior to NK cell infusion 8. Adequate liver function (ALT, AST and alkaline phosphatase \< 2 times ULN, bilirubin \< 1.5 times ULN), and adequate renal function (BUN or creatinine \< 1.5 times ULN) prior to NK cell 9. Must have recovered from the toxic effects of prior therapy (i.e., NCI-CTCEA version 5 grade 1 or less) 9a. An interval of at least 12 weeks must have elapsed since the completion of initial radiation therapy 9b. At least 6 weeks since the completion of any cytotoxic chemotherapy regimen 9c. For targeted agents only, patient should have recovered from any toxicity of the agent and have a minimum of 2 weeks since the last dose 9d. For patients who have received prior bevacizumab, at least 6 weeks is required before starting study treatment 10. Patients of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation Exclusion Criteria: 1. Patients with intra- or extra-CNS metastasis 2. Tumor involvement that would require ventricular, brainstem or posterior fossa injection or access through a ventricle or risk of ventricular penetration in order to deliver the NK cells 3. Tumors involving both hemispheres or those involving the subependyma or suspected CSF dissemination 4. Patients undergoing needle biopsies (Open biopsies are the minimum requirement for enrollment) 5. Pregnant or lactating patients 6. Patients on chronic corticosteroid therapy (except for replacement therapy) 7. Evidence of active uncontrolled infection or unstable or severe intercurrent medical conditions. All subjects must be afebrile at baseline (i.e., \< 38.0 Celsius \[C\]) 8. Any medical condition that precludes surgery 9. Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) \> 1.5 x ULN 10. Patients with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV), or an auto- immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible 11. Evidence of bleeding diathesis or use of anticoagulant medication or any medication which may increase the risk of bleeding. If the medication can be discontinued \>1 week prior to NK cell infusion then the subject may be eligible following consultation with the principal investigator (PI) 12. Subjects with significant systemic or major illnesses including but not limited to: congestive heart failure, ischemic heart disease, kidney disease or renal failure, organ transplantation, or significant psychiatric disorder 13. History or current diagnosis of any medical or psychological condition that in the Investigator's opinion, might interfere with the subject's ability to participate or inability to obtain informed consent because of psychiatric or complicating medical problems

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 24, 'type': 'ESTIMATED'}}

2023-03-27